The identification of prostate cancer predisposition genes has proven to be a challenge for the prostate research community. Although several predisposition loci have been identified, none of these localizations has led to gene isolation, and only one of these findings has been significantly validated (Neuhausen et al.,1999). In Utah we have very recently isolated the first prostate cancer predisposition gene (see Tavtigian et al, submitted, in Appendix), and some confirmatory evidence has already been observed (Rebbeck et al., submitted). During our over 10 years of prostate cancer research we have collected a resource of almost 300 high-risk prostate cancer pedigrees, with approximately 8,000 DNA samples stored. These significant prostate cancer resources and contributions are evidence of the importance of the Utah prostate cancer effort, which we hope to continue through this proposal. We have previously had NIH funding (1994- 1998), and funding through a partnership with Schering Plough (1997-2000); both have ended. Our collaboration with Myriad Genetics continues. We are in the process of finalizing a collaborative agreement between our group, Myriad Genetics, NIH and Johns Hopkins (letters of support will follow), that will result in an open exchange of data, results, and genomic and genetic resources from all groups, and which we hope will contribute significantly to prostate genetic research. This proposal supports the University of Utah high-risk pedigree collection and analysis, and some Myriad genotyping effort towards this goal.